Resveratrol inhibits the growth and induces the apoptosis of both normal and leukemic hematopoietic cells
Resveratrol inhibits the growth and induces the apoptosis of both normal and leukemic hematopoietic cells
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DOI：
10.1093/carcin/23.8.1327
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发表时间：
2002-08-01
期刊：
影响因子：
4.7
通讯作者：
Mossalayi, MD
中科院分区：
文献类型：
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作者：
Ferry-Dumazet, H;Garnier, O;Mossalayi, MD
人们通常认为反式 3,4',5-三羟基芪（白藜芦醇，RES）具有细胞生长调节和化学预防活性。然而，人们对这种多酚抑制肿瘤细胞生长的机制及其治疗潜力知之甚少。使用各种人类白血病细胞，我们首先确定了该化合物的抗肿瘤剂量。 RES抑制所有测试的淋巴和髓性白血病细胞的增殖并诱导细胞凋亡，IC50 = 5-43 muM。在细胞凋亡之前，RES 以剂量依赖性方式诱导 caspase 活性，细胞周期停滞在 G(2)/M 期，与细胞周期蛋白 A 和 B 的显着积累相关。RES 导致的白血病细胞死亡需要依赖 caspase 和不依赖 caspase 的蛋白酶，因为在这些培养物中同时添加 Z-VAD-FMK 和亮肽素可显着抑制 RES 的发生。虽然RES不影响未激活的正常淋巴细胞，但该药物在较低浓度下会降低循环正常人外周血淋巴细胞的生长并诱导细胞凋亡（IC50）
It is often postulated that trans-3,4',5-trihydroxystilbene (resveratrol, RES) exhibits cell growth regulatory and chemopreventive activities. However, mechanisms by which this polyphenol inhibits tumor cell growth, and its therapeutic potential are poorly understood. Using various human leukemia cells, we have first defined the anti-tumoral doses of this compound. RES inhibited the proliferation and induced the apoptosis of all tested lymphoid and myeloid leukemia cells with IC50 = 5-43 muM. Prior to apoptosis, RES-induced caspase activity in a dose-dependent manner and cell cycle arrest in G(2)/M-phase, correlating with a significant accumulation of cyclins A and B. Leukemia cell death with RES required both caspase-dependent and -independent proteases, as it was significantly inhibited by simultaneous addition of Z-VAD-FMK and leupeptin to these cultures. While RES did not affect non-activated normal lymphocytes, this agent decreased the growth and induced the apoptosis of cycling normal human peripheral blood lymphocytes at lower concentrations (IC50